Chronic Intestinal Pseudo-Obstruction: A Neuropathological Approach

Chronic intestinal pseudo-obstruction (CIPO) is a rare syndrome at the extreme end of severe functional bowel disorders. The clinical picture is characterized by a marked impairment of gut propulsive motility, thus mimicking a mechanical obstruction in the absence of any detectable organic cause constricting the gastrointestinal tract. CIPO is still a clinical challenge, and histopathology may be a valuable tool in the diagnostic workup. The histopathological correlates in CIPO include neural, interstitial cells of Cajal (ICC), and/or muscle abnormalities (hence, neuropathy, myopathy and ICC abnormalities), either alone or in combination. Apart from generating a diagnosis, detection of a given histopathological pattern may provide physicians with a guide to prognosis; thus, CIPO patients with an underlying myopathy usually have the poorest outcome compared to those with neuropathy or other patterns. Similar considerations can be applied to genetic forms of CIPO. Peculiar neuropathic/myopathic features, i.e. eosinophilic intraneuronal inclusions in enteric neurons, myenteric/submucosal ganglioneuromas of the enteric nervous system, and a more prominent involvement of the longitudinal rather than the circular layer throughout the gut may suggest CIPO of genetic origin. Another important aspect pertains to the identification of an immune-mediated/inflammatory neuropathy/leiomyositis that can be managed with immunosuppressive drugs. Although still inconclusive, the data published so far are promising and pave the way for future, well-designed trials to test the actual efficacy of immunosuppressive drugs in patients with CIPO due to an underlying inflammatory neuropathy. Future research on gut neuro-ICC-muscular abnormalities is expected to improve diagnostic and therapeutic strategies in patients with CIPO.